This invention relates to method and apparatus for assessing the electrical stability of the heart, and more particularly to the measurement of alternation of the morphology of electrocardiographic complexes which has a strong correlation with myocardial electrical stability.
Disturbances of electrical conduction processes in the heart are a major cause of morbidity and mortality. Sudden cardiac death, resulting from disturbances of electrical conduction in the heart, results in approximately 400,000 fatalities per year in the United States alone. The mechanism responsible for the great majority of sudden cardiac deaths is ventricular fibrillation, a disorganized pattern of electrical activity in the ventricles of the heart which leads to a disorganized pattern of mechanical contraction in the heart resulting in the cessation of effective pumping action and thus death. In addition, another disturbance of heart conduction processes, ventricular tachycardia, reduces the effectiveness of the pumping action of the heart. Ventricular tachycardia can thus cause loss of consciousness(syncope) or death. Even in cases where ventricular fibrillation itself does not cause death, ventricular tachycardia can degenerate into ventricular fibrillation which is lethal.
Effective means are now available to treat patients with electrical instabilities of the heart. For example, the internal programmed cardioverter/defibrillator is effective in preventing sudden cardiac death. This implanted device can terminate ventricular tachycardia and fibrillation by delivering an electric shock to the heart. Also antiarrhythmic drugs are available which modify the electrical properties of the heart. These drugs when used appropriately may render the heart electrically more stable; however, these drugs under other circumstances can also cause the heart to become more susceptible to ventricular tachycardia and fibrillation.
The first step in preventing sudden cardiac death is identifying individuals at risk. Currently, the procedure felt to be the most effective in identification of risk is invasive electrophysiologic testing. In this procedure catheter electrodes are advanced into the heart and by delivering electrical impulses to the heart a deliberate attempt is made to initiate ventricular tachycardia. This invasive procedure is only suitable for stratifying risk in individuals already known to be at high risk; commonly this procedure is used in individuals who have been successfully resuscitated from an episode of sudden cardiac death. This invasive procedure is also used to evaluate the effectiveness of antiarrhythmic drugs.
Clearly invasive electrophysiologic testing is not suitable for screening large populations of individuals for risk of serious ventricular arrhythmias. A variety of non-invasive measures have been used to stratify risk including measurement of the ejection fraction of the heart, measurement of the signal average electrocardiogram, measurement of heart rate variability, and measurement of ambient ventricular ectopic activity on a 24 hour electrocardiogram. These methods generally are not sufficiently predictive of risk to justify invasive testing or treatment of an asymptomatic individual.
Recently, a powerful non-invasive technique for assessing susceptibility to ventricular arrhythmias has been developed ("Method and Apparatus for Assessing Myocardial Electrical Stability" by R. J. Cohen and J. M. Smith, U.S. Pat. No. 4,802,491, February 1989; "Method and Apparatus for Quantifying Beat-to-Beat Variability in Physiologic Waveforms" by D. T. Kaplan and R. J. Cohen, U.S. Pat. No. 4,732,157, March 1988, "Fluctuations in T-Wave Morphology and Susceptibility to Ventricular Fibrillation" by D. R. Adam et. al., Journal of Electrocardiology, 17(3), 1984, 209-218; "Estimation of Ventricular Vulnerability to Fibrillation Through T-Wave Time Series Analysis" by D. R. Adam, S. Akselrod and R. J. Cohen, Computers in Cardiology 1981, 307-310; "Ventricular Fibrillation and Fluctuations in the Magnitude of the Repolarization Vector" by D. R. Adam et. al., Computers in Cardiology 1982, 241-244; "Period multupling-evidence for nonlinear behavior of the canine heart" by A. L. Ritzenberg, D. R. Adam and R. J. Cohen, Nature, 307, 1984, 159-161; "Subtle Alternating Electrocardiographic Morphology as an Indicator of Decreased Cardiac Electrical Stability" by J. M. Smith et. al., Computers in Cardiology 1985, 109-113; "Electrical alternans and cardiac electrical instability" by J. M. Smith et. al., Circulation, 77, 1988, 110-121; "The stochastic nature of cardiac electrical instability theory and experiment" by J. M. Smith, doctoral thesis, Massachusetts Institute of Technology, 1986; "Dynamic Tracking of Cardiac Vulnerability by Complex Demodulation of the T Wave" by B. D. Nearing, A. H. Huang and R. L. Verrier, Science, 252, 437-440; "Personal computer system for tracking cardiac vulnerability by complex demodulation of the T wave" by B. D. Nearing and R. L. Verrier, Journal of Applied Physiology, 74, 1993, 2606-2612). This technology involves quantifying a temporal pattern of subtle cycle-to-cycle variability in physiologic waveforms to assess physiologic stability, in particular this technology involves quantifying the temporal pattern of beat-to-beat variability in the electrocardiographic waveform to obtain a measure of the electrical stability of the heart. This variability is usually too small to be detected by visual inspection of the electrocardiogram and involves stochastic variability in waveform morphology from one cycle to another. In particular, a temporal pattern of variability of `alternans` is measured which corresponds to a variation in electrocardiographic waveforms on an every other beat basis, an ABABAB pattern of variability in waveform morphology. In order to make analysis of cycle-to-cycle variability in physiologic waveforms a practical clinical tool for the assessment of physiologic stability a number of improvements not taught in any of the references above are required.
One of the most significant limitations in the prior art regarding the use of physiologic waveform variability to assess myocardial electrical stability is the use of invasive electrical pacing of the heart. For example, in the human studies reported in Smith et. al. [1988, cited above] the heart was electrically paced by means of endocardial catheters to achieve a heart rate of between 100 and 150 beats per minute. Placing of these catheters into the heart is a highly invasive, risky, and expensive procedure and thus greatly limits the widespread applicability of this method to evaluating the risk of sudden death in patients.
Pacing the heart by means of catheters placed in the heart largely eliminates variability in the interbeat interval which is believed to interfere with development of electrical alternans. Previous attempts to measure electrical alternans in resting subjects not being paced, did not provide results which were predictive of susceptibility to ventricular arrhythmias. Therefore it was felt that pacing the heart by means of electrodes placed on the surface of the heart were required to make measurement of electrical alternans a useful predictive physiologic measure.
In addition the prior art for processing the recorded physiologic waveforms is limited, particularly in regard to its ability to assess subtle beat-to-beat variability in waveforms in the presence of intercycle interval variability, or abnormal heart-beats--such as premature atrial and ventricular beats, and to assess the statistical significance of a measured level of a temporal pattern of waveform variability such as alternans. The prior art for processing physiologic waveforms must be improved in order to make analysis of cycle-to-cycle variability in physiologic waveforms a practical clinical means of assessing physiologic stability in patients. Such improvements may be particularly necessary for preferred embodiments of the present invention that use means other than endocardial pacing for adjustment of heart rate, that may result in additional incidence of abnormal beats, or intercycle interval variability (the heart-beat interval variability is minimal during endocardial pacing), and introduce extrinsic noise which may complicate the interpretation of the statistical significance of a measured level of a temporal pattern of waveform variability.
It is an object of the present invention to provide a novel less-invasive method and apparatus for achieving the desired heart rate disclosed for the first time herein for the purpose of assessing physiologic stability from analysis of cycle-to-cycle variability in physiologic waveforms. It is further the object of the present invention to provide novel improvements in the processing of physiologic waveforms to permit the accurate assessment cycle-to cycle variability in physiologic waveforms under clinical conditions.